Astrocytic energy metabolism and glutamate formation - relevance for 13C-NMR spectroscopy and importance of cytosolic/mitochondrial trafficking
Astrocytic energy metabolism and glutamate formation - relevance for 13C-NMR spectroscopy and importance of cytosolic/mitochondrial trafficking
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DOI：
10.1016/j.mri.2011.04.013
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发表时间：
2011-12-01
影响因子：
2.5
通讯作者：
Hertz, Leif
中科院分区：
文献类型：
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作者：
Hertz, Leif
谷氨酸在c -13核磁共振（NMR）光谱测定脑内葡萄糖代谢中起双重作用。丙酮酸通过丙酮酸脱氢酶（PDH）形成最初未标记的谷氨酸和标记的α -酮戊二酸之间的双向交换表明了神经元（V-PDH,V- n）三羧酸（V- tca）循环中的能量代谢率，并进行了额外的计算，星形胶质细胞（V-PDH）也是如此。g)使用星形胶质细胞特异性底物[C-13]醋酸证实。在谷氨酸能活性增加的过程中，新谷氨酸分子的形成仅发生在星形胶质细胞中，通过联合丙酮酸羧化酶（V-PC）和星形胶质细胞PDH活性。V- pdh、V- g约占脑皮层总丙酮酸代谢的15%，V- pc约占10%。由于味精合成需要pdh生成和pc生成的丙酮酸盐，类似于20/25（80%）的星形胶质细胞丙酮酸代谢是通过谷氨酸形成进行的。净递质谷氨酸[γ -氨基丁酸（GABA）]的形成需要新合成的α -酮戊二酸转移到星形细胞细胞质中，α -酮戊二酸转氨化为谷氨酸，酰胺化为谷氨酰胺，谷氨酰胺转移到神经元，其水解为谷氨酸并释放谷氨酸（或GABA形成）。谷氨酸-谷氨酰胺循环，以谷氨酰胺合成速率（v周期）测量，也将先前释放的谷氨酸/GABA在初始星形细胞积累后转移到神经元，并主要测量谷氨酸信号传导。根据经验，葡萄糖代谢与V-cycle之间的比例类似于1/1，这可能反映了谷氨酸产生过程中与氧化/还原过程相关的葡萄糖利用，该过程与相关的转氨化过程一起，在信号活性增加停止后，通过随后的谷氨酸氧化来平衡。星形胶质细胞谷氨酸的形成和随后的氧化代谢提供了大量的三磷酸腺苷，用于神经元释放的K+和谷氨酸在细胞外间隙的积累，以及细胞质内Ca2+的稳态。(C) 2011爱思唯尔公司版权所有。
Glutamate plays a double role in C-13-nuclear magnetic resonance (NMR) spectroscopic determination of glucose metabolism in the brain. Bidirectional exchange between initially unlabeled glutamate and labeled alpha-ketoglutarate, formed from pyruvate via pyruvate dehydrogenase (PDH), indicates the rate of energy metabolism in the tricarboxylic acid (V-TCA) cycle in neurons (V-PDH,V- n) and, with additional computation, also in astrocytes (V-PDH. g), as confirmed using the astrocyte-specific substrate [C-13]acetate. Formation of new molecules of glutamate during increased glutamatergic activity occurs only in astrocytes by combined pyruvate carboxylase (V-PC) and astrocytic PDH activity. V-PDH,V- g accounts for similar to 15% of total pyruvate metabolism in the brain cortex, and V-PC accounts for another similar to 10%. Since both PDH-generated and PC-generated pyruvates are needed for glutamate synthesis, similar to 20/25 (80%) of astrocytic pyruvate metabolism proceed via glutamate formation. Net transmitter glutamate [gamma-aminobutyric acid (GABA)] formation requires transfer of newly synthesized alpha-ketoglutarate to the astrocytic cytosol, alpha-ketoglutarate transamination to glutamate, amidation to glutamine, glutamine transfer to neurons, its hydrolysis to glutamate and glutamate release (or GABA formation). Glutamate-glutamine cycling, measured as glutamine synthesis rate (V-cycle), also transfers previously released glutamate/GABA to neurons after an initial astrocytic accumulation and measures predominantly glutamate signaling. An empirically established similar to 1/1 ratio between glucose metabolism and V-cycle may reflect glucose utilization associated with oxidation/reduction processes during glutamate production, which together with associated transamination processes are balanced by subsequent glutamate oxidation after cessation of increased signaling activity. Astrocytic glutamate formation and subsequent oxidative metabolism provide large amounts of adenosine triphosphate used for accumulation from extracellular clefts of neuronally released K+ and glutamate and for cytosolic Ca2+ homeostasis. (C) 2011 Elsevier Inc. All rights reserved.